乙酰胆碱受体抗体阳性难治性全身型重症肌无力患者接受依库珠单抗治疗后的最小症状表现。
'Minimal symptom expression' in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab.
机构信息
Department of Neurology, Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Queen Elizabeth Neuroscience Centre and Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB, UK.
出版信息
J Neurol. 2020 Jul;267(7):1991-2001. doi: 10.1007/s00415-020-09770-y. Epub 2020 Mar 18.
BACKGROUND
The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension.
METHODS
Attainment of 'minimal symptom expression' was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. 'Minimal symptom expression' was defined as MG-ADL total score of 0-1 or MG-QOL15 total score of 0-3.
RESULTS
At REGAIN week 26, more eculizumab-treated patients achieved 'minimal symptom expression' versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension, the proportion of patients in the placebo/eculizumab group who achieved 'minimal symptom expression' increased after initiating eculizumab treatment and was sustained through 130 weeks of open-label eculizumab (MG-ADL: 1.7 to 27.8%; MG-QOL15: 1.7 to 19.4%). At extension study week 130, similar proportions of patients in the eculizumab/eculizumab and placebo/eculizumab groups achieved 'minimal symptom expression' (MG-ADL: 22.9% and 27.8%, respectively, p = 0.7861; MG-QOL15: 14.3% and 19.4%, respectively, p = 0.7531). The long-term tolerability of eculizumab was consistent with previous reports.
CONCLUSIONS
Patients with AChR+ refractory gMG who receive eculizumab can achieve sustained 'minimal symptom expression' based on patient-reported outcomes. 'Minimal symptom expression' may be a useful tool in measuring therapy effectiveness in gMG.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01997229, NCT02301624.
背景
在抗乙酰胆碱受体抗体阳性（AChR+）难治性全身性重症肌无力（gMG）的 26 周、3 期、随机、双盲、安慰剂对照的 REGAIN 研究及其开放标签扩展中，评估了依库珠单抗的疗效和耐受性。
方法
使用 gMG 症状的患者报告结局测量工具[重症肌无力日常生活量表（MG-ADL）、15 项重症肌无力生活质量问卷（MG-QOL15）]，在 REGAIN 完成时和开放标签扩展期间评估达到“最小症状表达”。“最小症状表达”定义为 MG-ADL 总分为 0-1 或 MG-QOL15 总分为 0-3。
结果
在 REGAIN 第 26 周，与安慰剂相比，更多的依库珠单抗治疗患者达到“最小症状表达”[MG-ADL：21.4%比 1.7%；差异 19.8%；95%置信区间（CI）8.5，31.0；p=0.0007；MG-QOL15：16.1%比 1.7%；差异 14.4%；95%CI 4.3，24.6；p=0.0069]。在开放标签扩展期间，安慰剂/依库珠单抗组中在开始依库珠单抗治疗后达到“最小症状表达”的患者比例增加，并在 130 周的开放标签依库珠单抗治疗中持续（MG-ADL：1.7%至 27.8%；MG-QOL15：1.7%至 19.4%）。在扩展研究第 130 周，依库珠单抗/依库珠单抗组和安慰剂/依库珠单抗组达到“最小症状表达”的患者比例相似（MG-ADL：分别为 22.9%和 27.8%，p=0.7861；MG-QOL15：分别为 14.3%和 19.4%，p=0.7531）。依库珠单抗的长期耐受性与先前的报告一致。
结论
接受依库珠单抗治疗的 AChR+难治性 gMG 患者可基于患者报告的结果实现持续的“最小症状表达”。“最小症状表达”可能是衡量 gMG 治疗效果的有用工具。
试验注册
ClinicalTrials.gov NCT01997229，NCT02301624。
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